Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.

Background: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting.

Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment.

Structural characterization and fermentation of a novel Moringa oleifera leaves polysaccharide with hypoglycemic effects.

Moringa oleifera leaf-derived natural products offer diverse health benefits in metabolic disorders. However, the structural attributes of M. oleifera leaf polysaccharides, their transformations during gastrointestinal digestion, and their influence on gut microbiota and hypoglycemic activity remain insufficiently understood.

Nonfatal hospital-treated pediatric and adolescent burn cases in the United States: A 2019-2022 National Electronic Injury Surveillance System analysis.

Burn injuries experienced by infants, children, and adolescents are prevalent and costly-psychologically, physically, and economically. Previous studies have acknowledged the dangers of pediatric burns; however, the literature was missing a thorough portrayal of the contemporary pediatric and adolescent burns landscape in the United States. The current study used 2019-2022 National Electronic Injury Surveillance System (NEISS) data to describe nonfatal pediatric and adolescent burn cases, including prevalence, burn type, body parts affected, product involvement, and differences by age and sex.

Building A Culturally Concordant Mentorship Program for Immigrant Premedical Students.

Objective: To develop an intervention addressing the unique needs of Afghan premedical students in successfully applying to and preparing for medical school in the U.S.

Design: A year-long virtual mentorship program was developed using the principles of community-based participatory research and cultural humility.

Upcycling textile derived microplastics waste collected from washer and dryers to carbonaceous products using hydrothermal carbonization.

Microplastics are an emerging pollutant of concern. Many microplastics in the waters arise from washing synthetic textiles in residential and commercial washing machines. The present research evaluated the upcycling of this waste to carbon materials by hydrothermal carbonization.

Family management of common sleep disturbances among children with autism: Implications for pediatric nursing research and practice.

Background: Sleep disturbances are common among children with autism spectrum disorder (ASD) and can negatively impact the health and wellbeing of the child, caregiver, and family. Nurses are well-positioned to support families of children with ASD to improve sleep.

Design & Purpose: In this mixed methods study, we leveraged an existing dataset to 1) characterize qualitative descriptions of sleep disturbances experienced by children (4-10y) with ASD, 2) examine the convergence of qualitative descriptions of sleep disturbances with quantitative scores on the Children's Sleep Habits Questionnaire (CSHQ), and 3) explore strategies used to manage bedtime and sleep disturbances.

Syncope among adolescents and young adults seeking treatment for cannabis-related injuries.

Importance: The legalization of cannabis for both recreational and medicinal purposes in numerous states across the United States has resulted in increased accessibility and usage rates. With Tetrahydrocannabinol (THC) potency in cannabis products on the rise, concerns regarding associated health implications, including syncope, have emerged.

Objective: This study aims to explore the prevalence and characteristics of cannabis-associated syncope among adolescents and young adults presenting to emergency departments (EDs).

Environmental factors driving microcystin contamination of estuarine bivalve populations downstream of freshwater cyanobacterial blooms.

Estuaries are dynamic environments that provide vital habitat to ecologically and commercially important bivalves. In some cases, freshwater tributaries can introduce cyanobacteria and associated cyanotoxins into estuaries that may subsequently accumulate in estuarine bivalves. Temporarily open/closed estuaries (TOCEs), which only experience tidal input for limited periods of time, may be particularly vulnerable to the accumulation of cyanotoxins in bivalves as they can be subject to freshwater input without tidal flushing and may experience lower salinities and cyanobacterial blooms.

Comparative analysis of hemp and wheat populations.

Fusarium head blight (FHB) has emerged as one of the most important diseases of hemp in the US. The disease has been documented in 4 out of 5 diagnostic regions and results in extensive blighting of flower and grain heads. Due to production similarities between grain hemp and agronomic crops, hemp is likely to be rotated with crops such as wheat as acreage increases.

: An alternative host for fungal pathogens attacking cultivated barley.

Wild grasses can serve as hosts for plant pathogens that attack small grain cereal crops, thereby perpetuating the disease cycle and potentially initiating epidemics. Foxtail barley () is a perennial grass species that is common across North America and can often be found growing near cultivated barley fields. Despite the close proximity of the two plant species in agro-ecosystems, few studies have been advanced to characterize the compatibility of to barley pathogens and its possible role in disease epidemiology.

Severity of charcoal rot disease in soybean genotypes inoculated with isolates differs among growth environments.

Charcoal rot of soybean caused by Macrophomina phaseolina (Mp) is a major disease of economic significance around the world. The objective of this test is to evaluate and identify new method(s) that can identify resistant and susceptible genotypes when inoculated with the fungus that causes charcoal rot in non-field environments. Four independent experiments were performed to determine the variability in disease severity when soybean genotypes are inoculated with isolates up to a total of 100 different variants of the charcoal rot fungus in laboratory, greenhouse, and growth chamber tests.

Genetic and epigenetic mechanisms of GPRC5D loss after anti-GPRC5D CAR T-cell therapy in multiple myeloma.

G protein-coupled receptor, class C, group 5, member D (GPRC5D) has emerged as a novel target for chimeric antigen receptor (CAR) T-cell therapy, demonstrating promising efficacy in multiple myeloma (MM). However, disease relapse is still common, and the mechanism of resistance remains poorly understood. In this study, we conducted whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) on MM samples from 10 patients who relapsed after GPRC5D CAR T-cell therapy.

Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study.

Rilzabrutinib is a covalent, reversible BTK inhibitor with multiple mechanisms targeting key immune thrombocytopenia (ITP) disease pathophysiology. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg bid (n=133) vs placebo (n=69) for 24 weeks. At baseline overall, median age was 47 years (range, 18-80), 63% female, 7.

Blunted CD40-responsive enhancer activation in CREBBP-mutant lymphomas can be restored by enforced CD4 T-cell engagement.

The CREBBP lysine acetyltransferase (KAT) is frequently mutated in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and has been studied using gene knock-out (KO) in murine and human cells. However, the majority of CREBBP mutations encode amino acid substitutions within the catalytic KAT domain (CREBBP KAT-PM) that retain an inactive protein and have not been extensively characterized. Using CRISPR gene editing and extensive epigenomic characterization of lymphoma cell-lines, we found that CREBBP KAT-PM lead to unloading of CREBBP from chromatin, loss of enhancer acetylation and prevention of EP300 compensation.

Loss of BCL7A Permits IRF4 Transcriptional Activity and Cellular Growth in Multiple Myeloma.

Multiple myeloma (MM) is a complex hematological malignancy characterized by genomic changes and transcriptomic dysregulation. Initial exome sequencing approaches have failed to identify any single frequent (>25%) mutation in the coding genome. However, using whole-genome sequencing (WGS), we found that one of the genomic regions most frequently mutated (62% of the MM patients) was the 5' untranslated (UTR) region and/or intron 1 of the BCL7A gene.

Itacitinib for the Prevention of IEC Therapy-Associated CRS: Results From the Two-Part Phase 2 INCB 39110-211 Study.

Cytokine release syndrome (CRS) and immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) are common complications following IEC therapy for hematologic malignancies. This two-part, phase 2 study (INCB 39110-211) investigated safety and efficacy of itacitinib, a potent, highly selective Janus kinase 1 inhibitor with broad anti-inflammatory activity, for prevention of CRS and ICANS in patients receiving commercial CD19-directed IEC therapy. Patients in part 1 received once-daily itacitinib 200 mg 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through Day 26, with guidelines for use of other CRS/ICANS interventions.

Lymphoid Malignancies in patients with Shwachman-Diamond Syndrome.

This study identified an increased risk of lymphoid malignancy in Shwachman-Diamond syndrome with an observed risk 38-fold higher than expected based on population data. Increased toxicity was observed with standard therapies in patients with SDS.

Beyond genotype: challenges in predicting disease risk for carriers of biallelic perforin variants.

Genetic screening for severe congenital immuno-hematological diseases offers potential for early intervention, particularly through preemptive allogeneic stem cell transplantation (HSCT). However, the clinical value of such screening depends on precise prognostic predictions based on genotype-phenotype correlations and/or functional confirmation. We investigated familial hemophagocytic lymphohistiocytosis type 2 (FHL2), caused by PRF1 variants.

Biology as vulnerability in follicular lymphoma: genetics, epigenetics, and immunogenetics.

Follicular lymphoma (FL) represents a heterogeneous group of B-cell neoplasms with distinct genetic, epigenetic, microenvironmental, and clinical features. It is the most prevalent indolent non-Hodgkin lymphoma, characterized by a relapsing course and risk of transformation to aggressive diffuse large B-cell lymphoma. Recent advances in high-throughput sequencing, spatial transcriptomics, and imaging technologies uncovered genetic, epigenetic, and immunogenetic features underpinning FL, offering insights into its biology and potential therapeutic vulnerabilities.

Impact of HLA Alloimmunization in Gene-Modified Autologous Stem Cell Transplant For Transfusion-Dependent Thalassemia.

We report our single center experience demonstrating that HLA Class I alloimmunization predicts longer time to platelet engraftment, increased bleeding complications and higher transfusion requirements in patients undergoing gene-modified hematopoietic stem cell transplant for transfusion-dependent beta thalassemia.

Proteostasis Disruption in Inherited Bone Marrow Failure Syndromes.

Inherited bone marrow failure syndromes (IBMFS) are genetic disorders of impaired hematopoiesis that manifest in childhood with both cytopenias and extra-hematologic findings. While several IBMFS are categorized as ribosomopathies due to shared underlying ribosomal dysfunction, there is a broader disruption of the protein homeostasis (proteostasis) network across both classic and emerging IBMFS. Precise regulation of the proteostasis network, including mechanisms of protein synthesis, folding, trafficking, and degradation as well as associated stress response pathways, has emerged as essential for maintaining hematopoietic stem cell (HSC) function, providing new potential mechanistic insights into IBMFS pathogenesis.

How I treat type 1 plasminogen deficiency.

Type 1 plasminogen deficiency (PLGD), an ultra-rare disorder caused by PLG pathogenic variants, results in decreased levels of immunoreactive and functional plasminogen. PLGD can cause fibrin-rich pseudomembranes on mucosa that impair tissue/organ function, impact quality of life, and are potentially life-threatening. Lesion regression/resolution is facilitated by intravenous administration of human plasma-derived Glu-plasminogen (IV PLG concentrate), the first and only FDA-approved specific treatment, licensed in 2021.

Single-cell panleukemia signatures of HSPC-like blasts predict drug response and clinical outcome.

The critical role of leukemic initiating cells as a therapy-resistant population in myeloid leukemia is well established, however, the molecular signatures of such cells in acute lymphoblastic leukemia remain underexplored. Moreover, their role in therapy response and patient prognosis is yet to be systematically investigated across various types of acute leukemia. We employed single-cell multiomics to analyze diagnostic specimens from 96 pediatric patients with acute lymphoblastic, myeloid, and lineage ambiguous leukemias.

Calcitriol Supplementation After Kidney Transplantation: Results of a Double-Blinded, Randomized, Placebo-Controlled Trial.

Background: A significant number of kidney transplant recipients have low BMD. We hypothesized that calcitriol administration over the first year post-transplantation would protect the cortical skeleton in recipients managed without corticosteroids by suppressing PTH and bone remodeling.

Methods: In this double-blind, placebo-controlled trial, 67 participants aged ≥18 years on corticosteroid-sparing immunosuppressive regimen were randomized to daily calcitriol 0.